Fei Huang1, Xu Liu2, Yongjing Cheng3, Xiaolin Sun2, Yingni Li2, Jing Zhao2, Di Cao4, Qin Wu5, Xiaoli Pan6, Haiteng Deng7, Mei Tian8, Zhanguo Li9. 1. Department of Nephrology and Rheumatology, Affiliated Hospital of Zunyi Medical University, Zunyi; Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing; and Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China. 2. Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China. 3. Department of Rheumatology and Immunology, Beijing Hospital, Beijing, China. 4. Department of Rheumatology and Immunology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 5. Key Laboratory of Basic Pharmacology of Ministry of Education & Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China. 6. Department of Nephrology and Rheumatology, Affiliated Hospital of Zunyi Medical University & Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China. 7. School of Life Sciences, Tsinghua University, Beijing, China. dht@tsinghua.edu.cn. 8. Department of Nephrology and Rheumatology, Affiliated Hospital of Zunyi Medical University & Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China. 348820517@qq.com. 9. Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China. li99@bjmu.edu.cn.
Abstract
OBJECTIVES: To identify novel autoantigens from circulating immune complexes (CICs) in rheumatoid arthritis (RA) patients and further explore their clinical significance. METHODS: From serum samples of 10 early RA (ERA) patients and 10 healthy donors, CICs were isolated and subjected to orbitrap mass spectrometry for autoantigen identification. Antibodies against the peptidoglycan recognition protein-2 (PGLYRP-2) derived from CICs were further detected by indirect enzyme-linked immunosorbent assay (ELISA) in 178 patients with RA, compared with 59 osteoarthritis (OA), 59 systemic lupus erythematosus (SLE), 55 ankylosing spondylitis (AS), 95 primary Sjögren's syndrome (pSS) and 50 healthy controls (HC). RESULTS: Thirty-three potential antigens out of 323 proteins were identified from CICs of RA patients. The autoantibodies to PGLYRP-2 were significantly increased in RA patients with 42.70% sensitivity and 85.20% specificity in comparison to other rheumatic diseases and healthy controls. The prevalence of anti-PGLYRP-2 was also elevated in subgroups of RA, with 34.72% in ERA, 35.29% in RF negative and 42.86% in anti-CCP negative patients. Further analysis suggested that anti-PGLYRP-2 was potentially accompanied with production of other autoantibodies in RA. In addition, we found by homology analysis that an epitope of PGLYRP-2442-447 mimics amino acid residues 431-436 of N-acetylmuramoyl-L-alanine amidase (NAMLAA) in actinomyces naeslundii. CONCLUSIONS: Autoantibody against PGLYRP-2 was identified as a promising biomarker in RA, especially in early and seronegative patients.
OBJECTIVES: To identify novel autoantigens from circulating immune complexes (CICs) in rheumatoid arthritis (RA) patients and further explore their clinical significance. METHODS: From serum samples of 10 early RA (ERA) patients and 10 healthy donors, CICs were isolated and subjected to orbitrap mass spectrometry for autoantigen identification. Antibodies against the peptidoglycan recognition protein-2 (PGLYRP-2) derived from CICs were further detected by indirect enzyme-linked immunosorbent assay (ELISA) in 178 patients with RA, compared with 59 osteoarthritis (OA), 59 systemic lupus erythematosus (SLE), 55 ankylosing spondylitis (AS), 95 primary Sjögren's syndrome (pSS) and 50 healthy controls (HC). RESULTS: Thirty-three potential antigens out of 323 proteins were identified from CICs of RA patients. The autoantibodies to PGLYRP-2 were significantly increased in RA patients with 42.70% sensitivity and 85.20% specificity in comparison to other rheumatic diseases and healthy controls. The prevalence of anti-PGLYRP-2 was also elevated in subgroups of RA, with 34.72% in ERA, 35.29% in RF negative and 42.86% in anti-CCP negative patients. Further analysis suggested that anti-PGLYRP-2 was potentially accompanied with production of other autoantibodies in RA. In addition, we found by homology analysis that an epitope of PGLYRP-2442-447 mimics amino acid residues 431-436 of N-acetylmuramoyl-L-alanine amidase (NAMLAA) in actinomyces naeslundii. CONCLUSIONS: Autoantibody against PGLYRP-2 was identified as a promising biomarker in RA, especially in early and seronegative patients.
Authors: Sidrah Jahangir; Peter John; Attya Bhatti; Muhammad Muaaz Aslam; Javaid Mehmood Malik; James R Anderson; Mandy J Peffers Journal: Life (Basel) Date: 2022-03-21